Method and apparatus for analyzing blood properties

ABSTRACT

Method and apparatus for determining the hematocrit and related properties of blood samples by determining the electrical conductance thereof. A sample probe is employed which has two spaced electrodes in the form of capillary tubes on either side of a nonconducting capillary tube. The probe forms an electrical resistivity measuring leg of an A-C bridge circuit and the unbalance of the circuit caused by replacement of a portion of a diluent by the blood sample is measured and transformed into the desired analysis.

United States Patent 1191 Louder et al.

1451 Nov. 13, 1973 METHOD AND APPARATUS FOR ANALYZING BLOOD PROPERTIESFiled:

Appl. No.: 243,182

Inventors: Nevitt M. Louder, Penn Hills;

Ronald Ferrie, Pittsburgh, both of v Pittsburgh, Pa.

Apr. 12, 1972 Assignee: Fisher Scientific Company,

U.S. c1. 324/30 R, 23/230 B, 12'8/21 1m. c1. G0ln 27/42 Field of Search324/29, 30 R, 30 B,

324/65, 65 P; 128/2 G, 2.1 E; 23/230 B References Cited UNITED STATESPATENTS 2/1965 Case ..324/30B PROBE BALANCE CIRCUIT GENERATOR 5/1966Okada 324/30 B 10/1972 Ur ..23/2302 Primary ExaminerMichael .1. LynchAttorney-John M. Webb [57] ABSTRACT Method and apparatus for determiningthe hematocrit and related properties of blood samples by determiningthe electrical conductance thereof. A sample probe is employed which hastwo spaced electrodes in the form of capillary tubes on either side of anonconducting capillary tube. The probe forms an electrical resistivitymeasuring leg of an A-C bridge circuit and the unbalance of the circuitcaused by replacement of a portion of a diluent by the blood'sam'p'le'is measured and transformed into the desired analysis.-

2 Claims, 4 Drawing Figures PATENTEDHBV 13 ms 3; 772 591 sum 10F 2 IO 3Mi F' 5 '4, i1

TIME IN SECONDS q- I Fig. 4

METHOD AND APPARATUS FOR ANALYZING BLOOD PROPERTIES The inventionrelates to blood testing and, more particularly, to a method andapparatus for automatically determining the hematocrit and relatedproperties.

There are several existing systems employed to measure the hematocrit ofa blood sample, which is the ratio, usually expressed in per cent, ofthe total volume of red cells to the total volume of the sample.

The conventional but time consuming system consists of centrifuging ablood sample in a test tube having a capillary size opening and afterthe red cells have collected at the bottom of the tube, measuring theheight of the packed cells and comparing that height with thetotalheight of the sample. The chance for human error is high with thisarrangement.

Another system measures hematocrit by means of an electrical conductancedetermination of a fixed volume of whole blood. This system has severaldrawbacks since the blood'electrolytes contained in the plasma alter theconductance value of the whole blood and is, therefore, detrimental toan expression of the hematocrit when the electrolyte level varies as isindicated in pathological specimens. In addition, the null balanceoperation of the bridge circuit employed does not effectively reflectthe portion of the instrumentation involved in the measure of thespecimen. Further, due to the viscous and tenacious nature of wholeblood, the bore of the specimen electrode requires thorough washoutbetween determinations.

The hematocrit is also measured indirectly by individually counting red'cells in a 50,000:l dilution while simultaneously measuring thecorpuscular volume. The hematocrit is then computed as the product ofthe total cell count and the mean cell volume. The actual measurement isalso an electrical conductance method in which the current densitieshave been judged as producing red cell volume distortions. This systemis subject to error in counting and in the dilution of the sample.Further, the isotonicity of the diluent and its distortion of the cellshape present further drawbacks.

Our invention substantially reduces the time to obtain a hematocritmeasurement as compared with the conventional centrifuging method. Ourinvention also provides accurate hematocrit measurements over all rangesof hematocrits. Further, our invention provides a minimum of diluent anda built-in means for sample probe washout between determinations. Andstill further, our invention permits pertinent null circuit obtentionand simplifies the determinations to eliminate chance for error.

Our invention is a method and apparatus for hematocrit and relatedproperty determination. The apparatus includes a capillary glass tubehaving spaced electrode end pieces, one of which is the end probe, andwhich form an electrical resistivity measuring leg of a bridge circuit.The probe initially contains all diluent and then a predetermined amountof blood sample is drawn therein and the electrical unbalance of thebridge circuit caused thereby is measured. The level of unbalance in theform of an A-C signal is amplified, filtered, rectified and amplifiedand then digitalized, counted, stored, etc. for demand print-out when ahematocrit or related calculable measurement such as mean corpuscularvolume is desired.

In the accompanying drawings, we have shown one preferred embodiment ofour invention in which:

FIG. 1 is a schematic partly in section of the hematocrit probe;

FIG. 2 is a section taken along section lines IlII of FIG. 1;

FIG. 3 is a block diagram of the hematocrit measurement system; and

FIG. 4 is a three stage, sequential representation of the settling ofthe blood sample in the diluent.

From the outset, it should be recognized that it.is known in the artthat the electrical conductance of whole blood is an accurate index ofthe bloods hematocrit and that our invention provides an improved methodand apparatus for making that determination. Therefore, othermeasurements relating to the hematocrit are also determinable from theelectrical conductance and are readily calculable therefrom.

The basic structure of our invention is the sample probe itself,generally designated 10, FIG. 1. The probe includes an outer protectivestainless steel jacket 11 and an inner concentric glass capillary tube12. Glass capillary tube 12 connects at one end to stainless steelcapillary end probe 13 through a section of Tygon tubing 14. End probe13, which acts as an electrode, is further held in place by nose piece15 which is ajdacent tubing' 14. Nose piece 15 is press fit into the endof jacket 11 and end probe 13 projects therethrough.

The upper end of capillary tube 12 is also connected by means of Tygontubing 16 to a stainless steel capillary tube 17 which forms the otherelectrode. The various tubes and tubing are supported by housing 18which has a cylindrical passage 19 through which protective jacket 11 issecured and stainless steel capillary tube 17 projects. An epoxyadhesive 20 placed in the open end of housing 18 further secures Tygontubing 16 and capillary tube 17 in place. Tube 17 extends through epoxyadhesive 20, is further secured by a quad ring 21 positioned atopadhesive 20 and connects to a pump system (not shown) for drawingsamples.

Terminals 22 and 26 are securably positioned through housing 18, FIG. 2.A thin electrode wire 25 extends from terminal 22 and connects as theground wire to stainless steel tube 17 and a thin electrode wire 24extends from terminal 26 and connects as the hot wire to stainless steelend probe 13. The hot wire 24 extends within protective steel jacket 11and along the glass tube 12.

The probe 10 can be employed with a number of existing samplingapparatus such as the Fisher Diluter Model 240 or the Fisher Hemalyzer,U.S. Pat. No. 3,537,794.

The circuitry which connects to the electrodes on the probe 10 isdepicted in block form in FIG. 3. The capillary glass tube 12 having thestainless steel end pieces 13 and 17 forms one resistive leg of an A-Cbridge circuit 30, termed Null Balance in FIG. 3. Bridge circuit 30 ispowered by a 400 cycle, 0-2 volt generator 31. The A-C signal caused bythe unbalance of bridge circuit 30 passes through operational amplifier32, is filtered by a 400 cycle filter 33 and rectified and amplified bya simple combination rectifier-amplifier 35. The measure ofrectification is read out on a Digital D-C voltmeter 36. Scope 34displays the A-C signal and serves as the manual adjustment of thebridge null conditions. The rectifier-amplifier 35 plus the bridgesource requires a +15 VDC, whereas the operational amplifier 32 requiresa -15 VDC, both of which are supplied by power source 37.

The operation of our invention is described hereinafter with respect toa specific trial run conducted. The probe is positioned with respect toa sample cup (not shown). Probe 10, between the electrodes, contains aliquid volume of 23.73 mm of a saline solution diluent received, forexample, from a diluter module. During positioning, the bridge null iselectronically established. The probe 10 descends into the sample andthe diluter module connected thereto pulls a 20 u-liter sample into theprobe. This 20 u-liter blood sample includes a volume of 11.26 mm up tothe first electrode and a volume of 8.74 mm between electrodes and,therefore, a resultant saline solution of 14.99 mm. As

the sample is being drawn, the A-C bridge is immedi' ately unbalanced.At the instant, the total whole blood sample is drawn or, when a signalis received for the probe to ascend from the sample cup, the bridgeunbalance signal is operationally amplified, filtered, rectified andamplified and then stored for print-out in the form of a hematocritreading or a mean corpuscular volume reading or any other relatedreading which is obtainable by means already known in the art. The probeis then flushed, the bridge null again electronically established andthe next determination is ready to begin.

The blood column within the capillary tube changes in the course oftime, thereby making the point in time when the bridge unbalance ismeasured a critical factor. This change of the blood column is depictedin FIG. 4 wherein column B represents a 10 sec. interval from column Aand column C represents a 10 sec. in terval from column B.

Column A represents the initial draw of blood into the diluent. Thecolumn of blood feathers to a filament within the envelope of diluent.The walls of the capillary tube 12 remain wetted by the diluent, therebyeliminating any deleterious effects caused by the blood sample adheringto the capillary tube wall. This further simplifies the flushingoperation which removes the blood sample and places a new charge ofdiluent in place. The column B of whole blood immediately begins tosettle and to a slight extend, the filament of whole blood segments.This blood settling continues as shown in column C with the passage ofadditional time. We have found that each 10 sec. interval changes thehematocrit measurement by increasing it by an amount of about 5 percent.Therefore, even though the amount of blood and diluent between theelectrodes is fixed, it is necessary to immediately measure the bridgeunbalance upon drawing the sample. In addition to the physicaldecomposition of the blood between the electrodes with respect to thediluent, temperature is critical and delaying the measurement may alsobe self-defeating due to the superimposed temperature drift. Therefore,it can be seen that an immediate measurement upon drawing a sample isessential.

We claim:

1. A method of analyzing properties of blood determinable from theelectrical conductance thereof comprising drawing a given amount ofdiluent into a sample probe, the sample probe including two spacedelectrodes in the form of capillary tubes positioned at opposing ends ofa nonconducting capillary tube and forming one electrical resistivitymeasuring leg of a balanced bridge circuit, replacing a portion of thediluent between the electrodes with a known amount of blood sample,measuring the unbalance of bridge caused by the replacement of thediluent with the blood, transforming the unbalance in the form of anelectrical signal into the desired blood analysis.

2. The method of claim 1 including measuring the unbalance of the bridgeimmediately upon replacing a portion of the diluent with the givenamount of blood sample.

1. A method of analyzing properties of blood determinable from theelectrical conductance thereof comprising drawing a given amount ofdiluent into a sample probe, the sample probe including two spacedelectrodes in the form of capillary tubes positioned at opposing ends ofa nonconducting capillary tube and forming one electrical resistivitymeasuring leg of a balanced bridge circuit, replacing a portion of thediluent between the electrodes with a known amount of blood sample,measuring the unbalance of bridge caused by the replacement of thediluent with the blood, transforming the unbalance in the form of anelectrical signal into the desired blood analysis.
 2. The method ofclaim 1 including measuring the unbalance of the bridge immediately uponreplacing a portion of the diluent with the given amount of bloodsample.